Speed limit on DNA-making sets pace for life's first steps

ScienceDaily | 3/14/2019 | Staff
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Scientists puzzled for two decades over this seemingly unnecessary withholding. Now researchers at Princeton University have shown that the inhibiting mechanism, controlled by an enzyme known as RNR, is actually key to the embryo's survival. Too much material early on leads to disaster for the fledgling lifeform.

"This study shows us how fragile development can be," said Stanislav Shvartsman, professor of chemical and biological engineering and the Lewis-Sigler Institute for Integrative Genomics at Princeton. "We asked the question, 'Why does the mother have to be so frugal?'" The problem led Shvartsman to test what happens when an embryo inherits an abundance of these building blocks. The answer was not pretty. "We realized, if you do not limit the supply, you create a temporal conflict that disrupts multiple processes in the embryo," he said.

Study - Journal - Current - Biology - March

In a study reported in the journal Current Biology on March 14, the team tracked two groups of flies' embryonic development: one with a normal supply of DNA building blocks, known as nucleotides, and one with around 10 times that amount. The results showed that, when more nucleotides were available to the embryo from the start, its DNA replication mechanism worked at breakneck speeds, running roughshod over the processes that followed and resulting in major defects later on.

Nareg Djabrayan, an associate research scholar at the Lewis-Sigler Institute for Integrative Genomics at Princeton and first author of the paper, likened the replication process to a machine. "When you provide that machine with too much of a certain input, its speed limit is broken," he said. "It goes too fast. And it messes with the other things that have to happen at the same time."

Problems - Step - Stages - Embryo

The problems that began in that first key step compounded through later stages. As the embryo...
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